The actin-cytoskeleton linker protein ezrin is regulated during osteosarcoma metastasis by PKC Journal Article
| Authors: | Ren, L.; Hong, S. H.; Cassavaugh, J.; Osborne, T.; Chou, A. J.; Kim, S. Y.; Gorlick, R.; Hewitt, S. M.; Khanna, C. |
| Article Title: | The actin-cytoskeleton linker protein ezrin is regulated during osteosarcoma metastasis by PKC |
| Abstract: | Ezrin is a member of the ERM (ezrin, radixin, moesin) protein family and links F-actin to the cell membrane following phosphorylation. Ezrin has been associated with tumor progression and metastasis in several cancers including the pediatric solid tumors, osteosarcoma and rhabdomyosarcoma. In this study, we were surprised to find that ezrin was not constitutively phosphorylated but rather was dynamically regulated during metastatic progression in osteosarcoma. Metastatic osteosarcoma cells expressed phosphorylated ERM early after their arrival in the lung, and then late in progression, only at the invasive front of larger metastatic lesions. To pursue mechanisms for this regulation, we found that inhibitors of PKC (protein kinase C) blocked phosphorylation of ezrin, and that ezrin coimmunoprecipitated in cells with PKCα, PKCι and PKCγ. Furthermore, phosphorylated forms of ezrin and PKC had identical expression patterns at the invasive front of pulmonary metastatic lesions in murine and human patient samples. Finally, we showed that the promigratory effects of PKC were linked to ezrin phosphorylation. These data are the first to suggest a dynamic regulation of ezrin phosphorylation during metastasis and to connect the PKC family members with this regulation. © 2009 Macmillan Publishers Limited All rights reserved. |
| Keywords: | osteosarcoma; controlled study; human tissue; protein expression; protein phosphorylation; bone neoplasms; human cell; cancer growth; nonhuman; animal cell; mouse; animals; mice; actin; animal tissue; animal experiment; animal model; cell line, tumor; wound healing; lung metastasis; gene expression regulation, neoplastic; regulatory mechanism; lung; neoplasm metastasis; immunoprecipitation; murinae; cell movement; protein kinase c; protein family; actins; cytoskeleton; cytoskeleton protein; sample; erm; ezrin; pkc; tumor metastasis; moesin; protein kinase c alpha; protein kinase c gamma; protein kinase c inhibitor; protein kinase c iota; radixin; osteosarcoma cell; cytoskeletal proteins |
| Journal Title: | Oncogene |
| Volume: | 28 |
| Issue: | 6 |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2009-02-12 |
| Start Page: | 792 |
| End Page: | 802 |
| Language: | English |
| DOI: | 10.1038/onc.2008.437 |
| PUBMED: | 19060919 |
| PROVIDER: | scopus |
| PMCID: | PMC7213760 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 9" - "Export Date: 30 November 2010" - "CODEN: ONCNE" - "Source: Scopus" |
